Our laboratories have much expertise in the areas of cellular immunology (Dr. Sarvetnick), viral immunity (Drs. Sarvetnick and Fox), and viral neuropathogenesis (Dr. Fox). Dr. Sarvetnick has investigated adaptive and innate immunity in relationship to spontaneous and induced autoimmune diseases, and in response to viral infection, using mouse models. She has had extensive experience with analysis of immune responses, and will perform the immune analyses in this proposal. Dr. Fox has studied viral and host immune aspects to the CNS disease induced by HIV, using the SIV-infected rhesus monkey model, and is a boardcertified pathologist. He will perform the viral analyses and histopathological analyses in this study. To insure our ability to work with flaviviruses in rodents, we obtained the Montana Myotis leukoencephalitis virus (MMLV) flavivirus(17) from the ATCC, amplified and titered the virus stock, and infected both SCID and immunocompetent mice. SCID mice developed encephalitis following intraperitoneal inoculation, whereas immunocompetent mice only developed encephalitis after intracranial inoculation. To insure rapid and efficient entry into the WNV field, we have set up a collaboration with Dr. M.A. Brinton (Georgia State University, Atlanta), a leading expert in the WNV field (see attached letter).